ObjectiveTo investigate the mechanism of Huangqin Tang （HQT） in regulating metabolic reprogramming during the inflammation-cancer transformation in colitis-associated colorectal cancer （CAC）. MethodsCAC mouse model was established using the carcinogen azoxymethane （AOM） combined with the inflammatory agent dextran sulfate sodium （DSS）. HQT treatment was adopted. Serum metabolomics analysis was performed at three stages （inflammation， proliferation， and tumor formation） using liquid chromatography-tandem mass spectrometry （LC-MS/MS） untargeted metabolomics coupled with multivariate statistical analysis to explore the mechanism of HQT intervention in metabolism in CAC. ResultsThe results revealed that HQT significantly reversed the disturbance of key metabolites in CAC mice. A total of 52， 67， and 45 differential metabolites were identified in the model group， compared to the normal group， during inflammation， proliferation， and tumor stages， respectively. Lactate， linoleic acid， oleic acid， elaidic acid， and betaine were characteristic metabolites persistently enriched throughout colitis-cancer transformation. Pathway enrichment analysis of differential metabolites showed that linoleic acid metabolism and arachidonic acid metabolism were the most significantly disturbed in CAC pathogenesis. The proliferation stage featured expanded amino acid metabolic networks， while the tumor stage uniquely exhibited two new pathways of nicotinate and nicotinamide metabolism and phosphoinositide metabolism. HQT exerted stage-specific regulatory effects： targeting arachidonic acid metabolism in the inflammation stage， correcting the dysregulation of choline-carnitine metabolism in the proliferation stage， and rescuing nicotinamide and tryptophan metabolic collapse in the tumor stage. ConclusionHQT exerts regulatory effects on metabolic disorders at various stages of the colitis-cancer transformation process， thereby effectively slowing the progression from colitis to cancer. The study also reveals the dynamic metabolic characteristics of colorectal "inflammation-cancer transformation，"providing new insights for research on the targeted mechanisms of traditional Chinese medicine in anti-tumor therapy based on metabolic reprogramming.

Objective To investigate the association between glycated albumin/hemoglobin A1c(GA/HbA1c)and type 2 diabetes mellitus(T2DM)complicated with metabolic associated fatty liver disease(MAFLD).Methods A total of 502 hospitalized T2DM patients were enrolled between January 2022 and December 2023 and divided into T2DM group(n=301)and combined with MAFLD(MAFLD,n=201)group.Clinical data were collected,and Logistic regression analyses were performed to evaluate the relationship between GA/HbA1c and MAFLD.Mediation analysis was conducted to assess the role of blood lipids.Results The MAFLD group had higher levels of drinking,waist-to-hip ratio,body mass index,fasting insulin,fasting C-peptide,insulin resistance index,alanine aminotransferase,aspartate aminotransferase,triglycerides(TG),small dense low-density lipoprotein(sdLDL),and blood uric acid compared to the T2DM group(P<0.05).The age,DM duration,GA,GA/HbA1c,and high-density lipoprotein cholesterol(HDL-C)were lower in the MAFLD group than in the T2DM group(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,GA/HbA1c was an influencing factor for the occurrence of MAFLD in T2DM patients.Mediation analysis revealed that TG,sdLDL,and HDL-C had significant mediating effects,accounting for 19.3%,12.4%,and 8.5%of the risk association,respectively.Conclusions GA/HbA1c is influencing factor of MAFLD in T2DM patients,with blood lipids showing significant mediating effects,suggesting that GA/HbA1c may serve as a novel indicator for assessing MAFLD risk.

Objective:To deeply understand the psychological experiences and needs of ward nurses caring for elderly patients with postoperative delirium, providing insights for improving their care capabilities.Methods:A descriptive qualitative study was conducted using purposive sampling to select nurses from the surgical wards of the Second Affiliated Hospital of Zhejiang University School of Medicine who had cared for elderly patients with postoperative delirium between January and March 2024. Semi-structured interviews were conducted, and traditional content analysis was used to extract themes.Results:Sixteen surgical ward nurses, aged 26-48 years old and all female, were interviewed. Four themes and nine sub-themes were identified: internal stress in caring for elderly patients with postoperative delirium (concerns about failing to recognize changes in condition, leading to delayed treatment; physical and psychological stress overwhelming nursing work); external challenges in caring for elderly patients with postoperative delirium (uncontrollable patient behavior; lack of close collaboration between medical staff; lack of awareness among patient families about postoperative delirium); lack of knowledge about postoperative delirium (difficulty in identifying subtypes of postoperative delirium; lack of knowledge about postoperative delirium management); and a desire for systematic professional support (urgent need for operational guidelines on postoperative delirium management in elderly patients; expectation for the establishment of a multidisciplinary team for postoperative delirium management in elderly patients).Conclusions:Nursing managers should pay attention to the physical and mental health of ward nurses, provide multifaceted support, strengthen their knowledge about postoperative delirium in elderly patients, optimize postoperative delirium management, and improve their care capabilities.

Objective To investigate the association between glycated albumin/hemoglobin A1c(GA/HbA1c)and type 2 diabetes mellitus(T2DM)complicated with metabolic associated fatty liver disease(MAFLD).Methods A total of 502 hospitalized T2DM patients were enrolled between January 2022 and December 2023 and divided into T2DM group(n=301)and combined with MAFLD(MAFLD,n=201)group.Clinical data were collected,and Logistic regression analyses were performed to evaluate the relationship between GA/HbA1c and MAFLD.Mediation analysis was conducted to assess the role of blood lipids.Results The MAFLD group had higher levels of drinking,waist-to-hip ratio,body mass index,fasting insulin,fasting C-peptide,insulin resistance index,alanine aminotransferase,aspartate aminotransferase,triglycerides(TG),small dense low-density lipoprotein(sdLDL),and blood uric acid compared to the T2DM group(P<0.05).The age,DM duration,GA,GA/HbA1c,and high-density lipoprotein cholesterol(HDL-C)were lower in the MAFLD group than in the T2DM group(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,GA/HbA1c was an influencing factor for the occurrence of MAFLD in T2DM patients.Mediation analysis revealed that TG,sdLDL,and HDL-C had significant mediating effects,accounting for 19.3%,12.4%,and 8.5%of the risk association,respectively.Conclusions GA/HbA1c is influencing factor of MAFLD in T2DM patients,with blood lipids showing significant mediating effects,suggesting that GA/HbA1c may serve as a novel indicator for assessing MAFLD risk.

Objective:To deeply understand the psychological experiences and needs of ward nurses caring for elderly patients with postoperative delirium, providing insights for improving their care capabilities.Methods:A descriptive qualitative study was conducted using purposive sampling to select nurses from the surgical wards of the Second Affiliated Hospital of Zhejiang University School of Medicine who had cared for elderly patients with postoperative delirium between January and March 2024. Semi-structured interviews were conducted, and traditional content analysis was used to extract themes.Results:Sixteen surgical ward nurses, aged 26-48 years old and all female, were interviewed. Four themes and nine sub-themes were identified: internal stress in caring for elderly patients with postoperative delirium (concerns about failing to recognize changes in condition, leading to delayed treatment; physical and psychological stress overwhelming nursing work); external challenges in caring for elderly patients with postoperative delirium (uncontrollable patient behavior; lack of close collaboration between medical staff; lack of awareness among patient families about postoperative delirium); lack of knowledge about postoperative delirium (difficulty in identifying subtypes of postoperative delirium; lack of knowledge about postoperative delirium management); and a desire for systematic professional support (urgent need for operational guidelines on postoperative delirium management in elderly patients; expectation for the establishment of a multidisciplinary team for postoperative delirium management in elderly patients).Conclusions:Nursing managers should pay attention to the physical and mental health of ward nurses, provide multifaceted support, strengthen their knowledge about postoperative delirium in elderly patients, optimize postoperative delirium management, and improve their care capabilities.

Objective:To establish the prediction model for postoperative delirium in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery.Methods:This was a nested case-control study. Seven hundred and fifty elderly patients of either sex with mild stroke, aged ≥65 yr, undergoing elective surgical procedures under general anesthesia in the Department of Gastrointestinal Surgery, Orthopedics and Urology at the Tangshan Workers Hospital from May to December 2023, were selected. The perioperative clinical data were collected. The incidence of postoperative delirium was assessed using the Confusion Assessment Scale 1-7 days after surgery or 1 day before discharge. The patients were assigned to the training set and the validation set in a ratio of 7∶3 using a simple random sampling method. Multivariate logistic regression was used to identify the risk factors for postoperative delirium, a postoperative delirium risk prediction model was established based on the risk factors, the nomogram was developed, and the receiver operating characteristic (ROC) curve, calibration curve and decision curve were plotted to assess the accuracy of the prediction model. The prediction model was verified using the validation set, and the calibration curve and ROC curve were plotted to assess the predictive performance of the model.Results:A total of 721 patients were finally included, and 108 patients developed postoperative delirium. Older age, high American Society of Anesthesiologists Physical Status classification, history of preoperative hypertension, short years of education, high preoperative Pittsburgh sleep quality index score, high preoperative National Institutes of Health Stroke Scale score, high intraoperative hypothermia, intraoperative hypotension and high postoperative numerical rating scale score were independent risk factors for postoperative delirium ( P<0.05). The area under the ROC curve of the training set prediction model was 0.996, with a sensitivity of 1.000, and specificity of 0.945. The slope of the calibration curve was close to 1, and the predicted risk of postoperative delirium was in good agreement with the actual risk. When the threshold probability of the decision curve was 0-0.9, the net return rate was higher than the null line. Validation set: In the calibration curve of the prediction model, the cohort and calibration curves were close to the ideal line, with an area under the ROC curve of 0.997, sensitivity of 1.000, and specificity of 0.962. Conclusions:Based on age, American Society of Anesthesiologists Physical Status classification, history of preoperative hypertension, years of education, preoperative Pittsburgh sleep quality index score, National Institutes of Health Stroke Scale score, intraoperative hypothermia and hypotension and postoperative numerical rating scale score, the prediction model for postoperative delirium is developed and has a good predictive performance in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery.

Background: Ulcerative colitis (UC) is a diffuse nonspecific intestinal inflammation. Spleen-kidney Yang deficiency combined with liver stagnation is the most common symptom. Sishen Pills-Tongxie Yaofang (SSP-TXYF) is a traditional Chinese medicine (TCM) that is widely used in the treatment of this symptom. However, its pharmacological mechanism and active components remain unclear. Objective: This study elucidated the potential mechanism and active components of SSP-TXYF in the treatment of UC from the perspective of TCM syndrome. Methods: Metascape, STRING, and Cytoscape were used to explore the SSP-TXYF-compound-target-UC network and biological enrichment pathways, so as to screen the active compounds, key targets, and pathways of SSP-TXYF. Through the construction of a rat model with UC, the key targets and active components were verified after SSP-TXYF administration. Results: A total of 77 effective active chemical components, 208 potential targets, and 5 core target genes were screened out. Gene Ontology biological process items and Kyoto Encyclopedia of Genes and Genomes signaling pathways showed that SSP-TXYF played a role in regulating nerve-endocrine, cell proliferation and apoptosis, and immune-related pathways. The main compounds and the target protein exhibited a good binding ability in molecular docking. The results of animal experiments showed that SSP-TXYF could improve UC through IL-6, AKT1, PTGS2, CASP3, and JUN, and nobiletin and wogonin were identified as the main active components. Conclusions: This study suggests that nobiletin and wogonin are the main components of SSP-TXYF in the treatment of UC, which provides effective therapeutic targets and drugs for future clinical treatment of UC.

ObjectiveTo induce the rat model of ulcerative colitis （UC） with spleen-kidney Yang deficiency and liver depression， and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang （SSW&TXYF） based on the therapeutic principles of tonifying spleen， soothing liver， warming kidney， and astringing intestine. MethodSixty male SD rats were randomized into normal， model， mesalazine， and high-， medium-， and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14， rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling， and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28， the rectal temperature was measured， and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg^-1 by gavage. Blood was sampled 1 h later， from which the serum was collected for measurement of the D-xylose content. The serum， hippocampus， and colorectum samples of rats were collected on day 29. The levels of gastrin （GAS）， adrenocorticotropic hormone （ACTH）， corticosterone （CORT）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， interleukin （IL）-4， tumor necrosis factor （TNF）-α， and interferon （IFN）-γ in the serum and 5-hydroxytryptamine （5-HT） in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， and c-Jun N-terminal kinase （JNK） in the colon tissue were determined by Real-time PCR and Western blot， respectively. ResultCompared with the normal group， the model group showed decreased body weight， anal temperature， and D-xylose content in the serum and increased GAS content （P<0.01）. The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum （P<0.01）， the preference for sucrose water， and the 5-HT content in the hippocampus （P<0.01）. Moreover， it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High， medium， and low doses of SSW&TXYF improved above indicators （P<0.05， P<0.01）， reduced inflammatory infiltration， and repaired the pathological damage of the tissue. Compared with the normal group， the model group showed lowered IL-4 level （P<0.01） and elevated TNF-α and IFN-γ levels （P<0.05， P<0.01） in the serum， as well as up-regulated expression of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. Compared with the model group， SSW&TXYF elevated the IL-4 level （P<0.01）， lowered the TNF-α and IFN-γ levels （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.

ObjectiveTo construct a mouse model of inflammation-associated colorectal cancer （CAC） by using azoxymethane （AOM）/dextran sulfate sodium （DSS） and investigate the effect of Huangqintang on the gut microbiota structure of mice during the occurrence and development of CAC by 16S rRNA gene high-throughput sequencing. MethodA total of 225 C57BL/6J mice were randomized into 5 groups （n=45）： Normal， model， positive drug （mesalazine）， and high （18 g·kg^-1） and low （9 g·kg^-1）-dose Huangqintang. Except those in the normal group， each mouse was injected with 10 mg·kg^-1 AOM on day 1 and day 5 within 1 week and then given 1.5% DSS solution for 7 days， which was then changed to sterile water for 14 days. This process referred to as one cycle， and mice were treated for a total of 3 cycles. On the first day of DSS treatment， mice were administrated with corresponding drugs by gavage， and the normal group and the model group were administrated with pure water by gavage， once a day until the end of the third cycle. The progression of CAC was divided into inflammation， proliferation， and tumorigenesis stages. At the end of each cycle， the body weight and colon length were measured for mice in each group， and the number of colon tumors in mice was recorded. Meanwhile， the disease activity index （DAI） was determined. The serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and carbohydrate antigen-199 （CA199）， a tumor marker in the gastrointestinal tract of mice， were measured by ELISA. Hematoxylin-eosin staining was employed to observe colon lesions. At the same time， 3-5 pellets of fresh feces of mice in the normal group， model group， and high-dose Huangqintang group were collected， from which the fecal DNA of mice was extracted for 16S rRNA gene high-throughput sequencing. ResultCompared with the normal group， the model group showed decreased body weight （P<0.01）， increased DAI， and shortened colon length （P<0.05） at the three stages. Compared with the normal group， the model group showed elevated levels of IL-1β， IL-6， and TNF-α （P<0.05） at the proliferation stage and elevated levels of CA199 at the inflammation， proliferation， and tumorigenesis （P<0.01） stages. Compared with the normal group， the model group presented obvious infiltration of inflammatory cells at the inflammation stage， thickening of the muscle layer and abnormal proliferation of mucosal layer cells at the proliferation and tumorigenesis stages， and final formation of advanced intraepithelial tumor lesions. Compared with the model group， the Huangqintang groups showed no significant improvement in the body weight， decreased DAI score， and increased colon length at the three stages， and the increase of colon length in the tumorigenesis stage was significant （P<0.01）. At the tumorigenesis stage， the administration of Huangqintang inhibited tumor formation and growth， reduced the number of tumors （P<0.01）， lowered the levels of IL-6 （P<0.05， P<0.01）， TNF-α （P<0.05， P<0.01）， and IL-1β at the three stages， and decreased CA199 at the inflammation stage as well as at the proliferation and tumorigenesis stages （P<0.01， P<0.05）. Compared with the model group， the administration of Huangqintang reduced inflammation and abnormal cell proliferation， delaying the occurrence of tumors. Compared with the normal group， the model group showcased decreased alpha and beta diversity and altered structure of gut microbiota at the inflammation， proliferation， and tumorigenesis stages. The administration of Huangqintang adjusted the abundance and diversity of gut microbiota to the normal levels. At the inflammation stage， Huangqintang positively regulated two differential phyla （Firmicutes and Bacteroidetes） and three differential genera （Muribaculaceae， Rikenellaceae_RC9_gut_group， and Flavonifractor） in mice. At the proliferation stage， Huangqintang positively regulated two differential phyla （Bacteroidetes and Patescibacteria） and five differential genera （Muribaculaceae， Rikenellaceae_RC9_gut_group， Candidatus_Saccharimonas， norank_f__UCG-010， and Allobaculum）. At the tumorigenesis stage， Huangqintang positively regulated two differential phyla （Proteobacteria and Patescibacteria） and eight differential genera （Muribaculaceae， Candidatus_Saccharimonas， norank_f_UCG-010， Lachnospiraceae_UCG-006， Allobaculum， Bacteroides， Lachnospiraceae_NK4A136_group， and Flavonifractor） in mice. ConclusionHuangqintang can intervene in the AOM/DSS-induced transformation of inflammation to CAC in mice by correcting inflammation and short-chain fatty acid-related microbiota disorders.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.